1. Field
The present invention is concerned with a novel process for the preparation of heterocyclic indene analogs, especially with the preparation of 4-hydroxycarbazole or N-protected 4-hydroxycarbazole. These compounds may be used as a building block for pharmaceutically active compounds, e.g. 1-(9H-carbazol-4-yloxy)-3-[[2-(2-methoxy -phenoxy)ethyl]amino]-2-propanol (carvedilol). This compound is known in the art and is described for example in EP 0 004920. It is especially useful for prophylaxis and treatment of heart- and circulatory diseases like, for example, hypertension, coronary heart failure, angina pectoris and the like.
2. Description
Processes for the catalytic cyclocarbonylation of pyrrole and indole derivatives have been described by Hiday et al., Advances in Metal-Organic Chemistry, Volume 4, 275–309. These processes are characterized by high temperatures, high catalyst loadings and modest selectivity. Moreover, the educts necessary for the reactions in these processes are expensive, since they have to be prepared by lengthy procedures, and are not available commercially.
Surprisingly, it has been found that using the process according to the present invention, heterocyclic indene analogs, e.g. indole or carbazole derivatives (such as 4-hydroxycarbazole and N-protected 4-hydroxycarbazole) can be prepared from commercial educts and without the aforementioned disadvantages.